Manuel Garcia Basallote

The failure of the therapeutic administration of superoxide dismutase (SOD) and catalase (CAT) enzymes to prevent oxidative stress has fostered the development of metal complexes that are capable of mimicking their activity. In the present work, two new pyridine azacyclophane ligands capable of coordinating Cu²⁺ and Fe²⁺ to give rise to mimetics with high activities toward disproportionation of the superoxide anion or hydrogen peroxide, depending on the metal ion, have been prepared. Although the Cu²⁺ complexes have some of the highest SOD activities reported to date, they are completely inactive toward H₂O₂ disproportionation. In contrast, the Fe²⁺ complexes catalyze the disproportionation of H₂O₂ without showing any catalytic SOD activity. Therefore, the type of antioxidant activity of these macrocycles is dictated by the nature of the metal ion, which represents a new approach to the development of potentially useful mimetics.

Semihydrogenation of internal alkynes catalyzed by the air-stable imidazolyl amino [Mo₃S₄Cl₃(ImNH₂)₃]⁺ cluster selectively affords the (Z)-alkene under soft conditions in excellent yields. Experimental results suggest a sulfur-based mechanism with the formation of a dithiolene adduct through interaction of the alkyne with the bridging sulfur atoms. However, computational studies indicate that this mechanism is unable to explain the experimental outcome: mild reaction conditions, excellent selectivity toward the (Z)-isomer, and complete deuteration of the vinylic positions in the presence of CD₃OD and CH₃OD. An alternative mechanism that explains the experimental results is proposed. The reaction begins with the hydrogenation of two of the Mo₃(μ₃-S)(μ-S)₃ bridging sulfurs to yield a bis(hydrosulfide) intermediate that performs two sequential hydrogen atom transfers (HAT) from the S-H groups to the alkyne. The first HAT occurs with a spin change from singlet to triplet. After the second HAT, the singlet state is recovered. Although the dithiolene adduct is more stable than the hydrosulfide species, the large energy required for the subsequent H₂ addition makes the system evolve via the second alternative pathway to selectively render the (Z)-alkene with a lower overall activation barrier.

[Fe^II(TSC)₂] complexes selectively catalyze oxidation of styrene to benzaldehyde with H₂O₂. These iron complexes, the free TSC ligands, and [Zn(Dp44mT)₂] also catalyze sulfoxidation of thioanisole, but only the iron complexes catalyze styrene oxidation.

Efficient protocols for the semihydrogenation of internal alkynes and terminal alkynols are reported using the new [Mo₃S₄Cl₃(ImNH₂)₃]⁺ complex as catalyst.

Two oxoiron(IV) isomers (^R2a and ^R2b) of general formula [Fe^IV(O)(^RPyNMe₃)(CH₃CN)]²⁺ are obtained by reaction of their iron(II) precursor with NBu₄IO₄. The two isomers differ in the position of the oxo ligand, cis and trans to the pyridine donor. The mechanism of isomerization between ^R2a and ^R2b has been determined by kinetic and computational analyses uncovering an unprecedented path for interconversion of geometrical oxoiron(IV) isomers. The activity of the two oxoiron(IV) isomers in hydrogen atom transfer (HAT) reactions shows that ^R2a reacts one order of magnitude faster than ^R2b, which is explained by a repulsive noncovalent interaction between the ligand and the substrate in ^R2b. Interestingly, the electronic properties of the R substituent in the ligand pyridine ring do not have a significant effect on reaction rates. Overall, the intrinsic structural aspects of each isomer define their relative HAT reactivity, overcoming changes in electronic properties of the ligand.

Two oxoiron(IV) isomers (^R2a and ^R2b) of general formula [Fe^IV(O)(^RPyNMe₃)(CH₃CN)]²⁺ are obtained by reaction of their iron(II) precursor with NBu₄IO₄. The two isomers differ in the position of the oxo ligand, cis and trans to the pyridine donor. The mechanism of isomerization between ^R2a and ^R2b has been determined by kinetic and computational analyses uncovering an unprecedented path for interconversion of geometrical oxoiron(IV) isomers. The activity of the two oxoiron(IV) isomers in hydrogen atom transfer (HAT) reactions shows that ^R2a reacts one order of magnitude faster than ^R2b, which is explained by a repulsive noncovalent interaction between the ligand and the substrate in ^R2b. Interestingly, the electronic properties of the R substituent in the ligand pyridine ring do not have a significant effect on reaction rates. Overall, the intrinsic structural aspects of each isomer define their relative HAT reactivity, overcoming changes in electronic properties of the ligand.

Formic acid (FA) dehydrogenation is an attractive process in the implementation of a hydrogen economy. To make this process greener and less costly, the interest nowadays is moving toward non-noble metal catalysts and additive-free protocols. Efficient protocols using earth abundant first row transition metals, mostly iron, have been developed, but other metals, such as molybdenum, remain practically unexplored. Herein, we present the transformation of FA to form H-2 and CO2 through a cluster catalysis mechanism mediated by a cuboidal [Mo3S4H3(dmpe)(3)](+) hydride cluster in the absence of base or any other additive. Our catalyst has proved to be more active and selective than the other molybdenum compounds reported to date for this purpose. Kinetic studies, reaction monitoring, and isolation of the [Mo3S4(OCHO)(3)(dmpe)(3)](+) formate reaction intermediate, in combination with DFT calculations, have allowed us to formulate an unambiguous mechanism of FA dehydrogenation. Kinetic studies indicate that the reaction at temperatures up to 60 degrees C ends at the triformate complex and occurs in a single kinetic step, which can be interpreted in terms of statistical kinetics at the three metal centers. The process starts with the formation of a dihydrogen-bonded species with Mo-H center dot center dot center dot HOOCH bonds, detected by NMR techniques, followed by hydrogen release and formate coordination. Whereas this process is favored at temperatures up to 60 degrees C, the subsequent beta-hydride elimination that allows for the CO2 release and closes the catalytic cycle is only completed at higher temperatures. The cycle also operates starting from the [Mo3S4(OCHO)(3)(dmpe)(3)](+) formate intermediate, again with preservation of the cluster integrity, which adds our proposal to the list of the infrequent cluster catalysis reaction mechanisms.

The novel [W₃S₄H₃(edpp)₃]⁺ (edpp=(2‐aminoethyl)diphenylphosphine) (1⁺) cluster hydride with an acidic −NH₂ functionality has been synthetized and studied. Its crystal structure shows the characteristic incomplete W₃S₄ cubane core with the outer positions occupied by the P and N atoms of the edpp ligands. Although no signal due to the hydride ligands is observed in the ¹H NMR spectrum, hydride assignment is supported by ¹H‐¹⁵N HSQC techniques, the changes in the ³¹P{¹H} NMR chemical shift, and FT‐IR spectra in the W−H region of the deuterated [W₃S₄D₂H(edpp)₃]⁺ (1⁺‐d₂) samples. Moreover, all NMR evidences suggest that one of the hydrogen atoms of the NH₂ group in 1⁺ is rapidly exchanging with the hydride. The reaction of 1⁺ with acids (HCl, HBr and DCl) features complex polyphasic kinetics with zero‐order dependence with respect to the acid concentration, being also independent of the solvent nature. This behavior differs from that of their diphosphino analogues, suggesting a different mechanism.

Oxoiron(IV) complexes bearing tetradentate ligands have been extensively studied as models for the active oxidants in non‐heme iron‐dependent enzymes. These species are commonly generated by oxidation of their ferrous precursors. The mechanisms of these reactions have seldom been investigated. In this work, the reaction kinetics of complexes [Fe^II(CH₃CN)₂L](SbF₆)₂ ([1](SbF₆)₂ and [2](SbF₆)₂) and [Fe^II(CF₃SO₃)₂L] ([1](OTf)₂ and [2](OTf)₂ (1, L=^Me,HPytacn; 2, L=^nP,HPytacn; ^R,R′Pytacn=1‐[(6‐R′‐2‐pyridyl)methyl]‐4,7‐ di‐R‐1,4,7‐triazacyclononane) with Bu₄NIO₄ to form the corresponding [Fe^IV(O)(CH₃CN)L]²⁺ (3, L=^Me,HPytacn; 4, L=^nP,HPytacn) species was studied in acetonitrile/acetone at low temperatures. The reactions occur in a single kinetic step with activation parameters independent of the nature of the anion and similar to those obtained for the substitution reaction with Cl⁻ as entering ligand, which indicates that formation of [Fe^IV(O)(CH₃CN)L]²⁺ is kinetically controlled by substitution in the starting complex to form [Fe^II(IO₄)(CH₃CN)L]⁺ intermediates that are converted rapidly to oxo complexes 3 and 4. The kinetics of the reaction is strongly dependent on the spin state of the starting complex. A detailed analysis of the magnetic susceptibility and kinetic data for the triflate complexes reveals that the experimental values of the activation parameters for both complexes are the result of partial compensation of the contributions from the thermodynamic parameters for the spin‐crossover equilibrium and the activation parameters for substitution. The observation of these opposite and compensating effects by modifying the steric hindrance at the ligand illustrates so far unconsidered factors governing the mechanism of oxygen atom transfer leading to high‐valent iron oxo species.